This invention relates generally to basement membranes and specifically to a novel tissue-specific basement membrane-associated protein.
Basement membranes are thin sheets of extracellular matrix separating epithelial cells from underlying tissue stroma. They compartmentalize epithelial and endothelial organs and maintain tissue structures. In some tissues the basement membrane is a product of the interaction of several cell types; for example, the glomerular basement membrane is made by both epithelial and endothelial cells. In skeletal muscle, fibroblasts from the endomysium contribute type IV collagen to the assembly of the basement membrane. The formation of the neural basal lamina requires the interaction of Schwann cells and neurons. Further, basement membranes function in development and tissue repair by promoting attachment, migration and proliferation of cells and by mediating signals for tissue interactions.
All basement membranes contain laminin, type IV collagen, entactin and heparan sulfate proteoglycan. Laminin is a large glycoprotein composed of three polypeptide chains, a 400 kD A chain and two B chains of about 200 kD. The amino-terminal two thirds of the A chain is homologous to the B1 and B2 chains while the carboxy-terminal third has a distinct structure. Laminin promotes attachment, spreading, motility and growth of a variety of cell types. One of the most striking features of laminin is its capacity to promote outgrowth of neurites from cultured neuronal cells. A major site of cell adhesion and the neurite-promoting activity appear to reside in the globular domain at the end of the long arm of this molecule.
The metastatic propensity of certain tumor cells may also be influenced by laminin. For example, laminin has been shown to mediate the attachment of malignant carcinoma cells to type IV collagen and to increase the metastatic potential of murine melanoma cells. Other basement membrane proteins and their receptors may be involved in the adhesion of metastasizing tumor cells to basement membranes of blood vessels and other epithelial tissues.
The Leivo and Engvall reference, Proc. Natl. Acad. Sci. USA, 85: 1544-1548 (1988), incorporated by reference herein, recently described the isolation of a 65-kDa and an 80-kDa precursor, basement membrane-associated protein which was termed merosin. However, there was no disclosure of the approximately 800 kDa protein described herein. Since this 65-kDa and 80-kDa proteins appear to be subunits of the 800 kDa protein, the term "merosin" has now also been applied to the 800 kDa protein described herein.
Because of the critical role of basement membranes in development, tissue repair, neurite growth and cancer, there exists a need for the identification of new basement membrane components. The present invention satisfies this need.